Introduction: Hyponatremia of varying severity is a fairly common disorder of water homeostasis encountered in the practice of internal medicine and has a variety of etiologies. Here we present a case of refractory hyponatremia secondary to an uncommon endocrine disorder. Case description: Our patient, a 55-year-old woman with a known case of hypothyroidism for 5 years, presented with complaints of moderate, symptomatic, and persistent hyponatremia. An evaluation revealed chronic euvolemic hyponatremia refractory to 3% saline. Further workup to rule out the syndrome of inappropriate antidiuretic hormone (SIADH) revealed panhypopituitarism with partial empty sella (PES). Discussion: Though usually not associated with any hormonal deficiency, rarely PES is associated with a deficiency of one or more pituitary hormones. Equally rare is the syndrome of euvolemic hyponatremia secondary to empty sella syndrome with hypopituitarism. Panhypopituitarism can have life-threatening consequences if left undiagnosed and untreated. Conclusion: In any case of euvolemic hyponatremia, it is important to work up for hypopituitarism as a rare cause before ruling in SIADH.